Vasculogenic mimicry (VM) contributes to the resistance of anti-angiogenic therapies in glioma. Certain genes, including MMP-2 and VEGF may be associated with the development of VM. Astrocyte elevated gene-1 (AEG-1) is considered to be an oncogene that promotes autophagy, invasion, metastasis, angiogenesis and drug resistance; however, the association between AEG-1 and VM formation is still unknown. The present study investigated the effects of AEG-1 downregulation on VM formation in the U87 glioma cell line and in xenograft models of glioma, and the potential underlying mechanisms of action. In the present study, U87 glioma cells were infected with the AEG-1 short hairpin RNA lentivirus. A Matrigel-based tube formation assay was performed to evaluate VM formation . Reverse transcription-quantitative PCR and western blot analysis were conducted to investigate the mRNA and protein expression levels of MMP-2 and VEGF. Glioma xenograft models were generated through the intracerebral implantation of U87 glioma cells into nude rats; CD34/Periodic Acid-Schiff double-staining was performed to detect VM channels . Following AEG-1 downregulation in U87 cells, the development of VM was significantly decreased and . In addition, the expression levels of MMP-2 and VEGF in glioma cells were decreased compared with the control group. These results suggested that downregulation of AEG-1 expression could significantly inhibit the development of VM in gliomas, both and , and may be partially related to the regulation of VEGF and MMP-2 expression.
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http://dx.doi.org/10.3892/etm.2020.9454 | DOI Listing |
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School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, People's Republic of China.
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Department of Biology, School of Medicine, State University of Rio de Janeiro, Professor Manuel de Abreu, 444, Avenue, Rio de Janeiro 20550-170, Brazil.
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